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Title: Crystal structure of the Rous sarcoma virus intasome

Integration of the reverse-transcribed viral DNA into the host genome is an essential step in the life cycle of retroviruses. Retrovirus integrase catalyses insertions of both ends of the linear viral DNA into a host chromosome. Integrase from HIV-1 and closely related retroviruses share the three-domain organization, consisting of a catalytic core domain flanked by amino- and carboxy-terminal domains essential for the concerted integration reaction. Although structures of the tetrameric integrase–DNA complexes have been reported for integrase from prototype foamy virus featuring an additional DNA-binding domain and longer interdomain linkers, the architecture of a canonical three-domain integrase bound to DNA remained elusive. In this paper, we report a crystal structure of the three-domain integrase from Rous sarcoma virus in complex with viral and target DNAs. The structure shows an octameric assembly of integrase, in which a pair of integrase dimers engage viral DNA ends for catalysis while another pair of non-catalytic integrase dimers bridge between the two viral DNA molecules and help capture target DNA. The individual domains of the eight integrase molecules play varying roles to hold the complex together, making an extensive network of protein–DNA and protein–protein contacts that show both conserved and distinct features compared with thosemore » observed for prototype foamy virus integrase. Finally, our work highlights the diversity of retrovirus intasome assembly and provides insights into the mechanisms of integration by HIV-1 and related retroviruses.« less
Authors:
 [1] ;  [1] ;  [2] ;  [3] ;  [3] ;  [3] ;  [1]
  1. Univ. of Minnesota, Minneapolis, MN (United States). Dept. of Biochemistry, Molecular Biology and Biophysics. Inst. for Molecular Virology. Masonic Cancer Center
  2. Cornell Univ., Lemont, IL (United States). Advanced Photon Source. Northeastern Collaborative Access Team
  3. Saint Louis Univ., St. Louis, MO (United States). Health Sciences Center. Inst. for Molecular Virology
Publication Date:
OSTI Identifier:
1239418
Grant/Contract Number:
AC02-06CH11357; P41 GM103403; GM109770; AI087098; AI100682
Type:
Accepted Manuscript
Journal Name:
Nature (London)
Additional Journal Information:
Journal Name: Nature (London); Journal Volume: 530; Journal Issue: 7590; Journal ID: ISSN 0028-0836
Publisher:
Nature Publishing Group
Research Org:
Univ. of Minnesota, Minneapolis, MN (United States)
Sponsoring Org:
USDOE Office of Science (SC); National Inst. of Health (NIH) (United States)
Contributing Orgs:
Cornell Univ., Lemont, IL (United States). Advanced Photon Source; Saint Louis Univ., St. Louis, MO (United States)
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; X-ray crystallography; Retrovirus; DNA; DNA-binding proteins